3例甲巯咪唑致粒细胞缺乏症合并感染的治疗分析

目的探讨甲巯咪唑治疗甲状腺功能亢进引起粒细胞缺乏症的临床特点及治疗对策。方法回顾分析某大型综合医院内分泌科收治的因使用甲巯咪唑致粒细胞缺乏症3例住院病例的临床资料。结果甲巯咪唑所致的粒细胞缺乏症多出现于用药的1³个月内,临床表现为发热、咽痛、乏力等症状,严重的出现败血症;早期发现,早期治疗,经验性使用广谱抗菌药物和升白细胞药物能提高抢救成功率。结论甲巯咪唑可导致白细胞和粒细胞减少;用药前后应密切监测血常规,一旦出现粒细胞缺乏,立即停药,并采取积极的综合治疗措施。     

治疗1例甲巯咪唑致粒细胞缺乏症病例报道

通过1例甲巯咪唑致粒细胞缺乏症病例分析,探讨药物致粒细胞严重缺乏患者升白细胞治疗的用药经验。     

他巴唑致粒细胞缺乏症14例分析

抗甲状腺药物他巴唑是治疗甲状腺功能亢进症的最常用药物,副作用较多,其中较为严重的是粒细胞缺乏症。我院于1991～2000年共收治他巴唑致粒细胞缺乏症14例,现分析如下。     

10例抗甲状腺药物致粒细胞缺乏伴重症感染的临床观察

目的:观察头孢哌酮钠他唑巴坦钠联合阿米卡星治疗抗甲状腺药物致粒细胞缺乏症伴重症感染的临床疗效和安全性。方法:10例因抗甲状腺药物所致粒细胞缺乏并重症感染的患者,静脉滴注头孢哌酮钠他唑巴坦钠2.0g/次,1次/12h;阿米卡星静脉滴注0.6g/次,1次/d,两药疗程7d～10d。结果:痊愈5例,显效2例,进步2例,无效1例,总有效率70%;2例出现不良反应,主要为胃肠反应,未经处理症状逐渐消失。结论:头孢哌酮钠他唑巴坦钠联合阿米卡星治疗抗甲状腺药物致粒细胞缺乏伴重症感染疗效明显,患者耐受性好,可作为经验性治疗中性粒细胞缺乏伴感染患者的首选方案。     

粒细胞集落刺激因子治疗抗甲状腺功能亢进症药物致粒细胞缺乏症的疗效研究

目的 观察粒细胞集落刺激因子(G-CSF)治疗抗甲状腺功能亢进症药物(ATD)致粒细胞缺乏症的疗效.方法 回顾性分析15例因ATD引起粒细胞缺乏症患者的临床资料,比较G-CSF治疗与糖皮质激素治疗的疗效.结果 G-CSF治疗组的患者粒细胞恢复正常的时间和住院时间均显著短于糖皮质激素治疗组[(7.1±4.2)d与(12.9±5.4)d、(10.4±6.4)d与(18.3±3.9)d,均P＜0.05].14例患者治愈,1例死于重度感染.结论 ATD致粒细胞缺乏症的患者经G-CSF治疗,能够有效缩短粒细胞恢复的时间,减少住院时间.     

1例甲巯咪唑致粒细胞缺乏症患者的药学监护

目的通过回顾1例甲状腺功能亢进患者应用甲巯咪唑致粒细胞缺乏症的诊疗过程的,探讨药师如何依据患者的病理生理情况完成药学监护。方法药师与临床医师密切配合,预估重组人粒细胞刺激因子治疗粒细胞缺乏症的治疗终点、合理选择和调整抗菌药物的品种、根据肾功能状况确定给药剂量,以及对患者进行的用药教育。结果患者共住院28d,粒细胞缺乏症得到纠正,感染得到控制,顺利地完成了131I放射治疗。结论临床药师加入临床治疗团队,提供药学服务可以提高临床药物治疗效果。     

一例头孢哌酮钠舒巴坦钠致粒细胞缺乏症患者的药学监护

头孢哌酮钠舒巴坦钠致粒细胞缺乏症是临床较少见的不良反应。临床药师通过参与一例慢性阻塞性肺疾病急性加重期伴高血压患者应用头孢哌酮钠舒巴坦钠致粒细胞缺乏症的治疗全过程,协助医师为患者制订个体化药物治疗方案,监测患者在治疗过程中出现的药品不良反应,并对不良反应的处理方案提出药学建议,为患者提供了个体化的药学监护。临床药师通过药学监护参与临床治疗,可有效促进临床药物治疗的安全性和有效性。     

糖皮质激素治疗抗甲状腺药物致粒细胞缺乏症的临床研究

目的探讨糖皮质激素治疗抗甲状腺药物致粒细胞缺乏症的临床效果,旨在降低甲状腺功能亢进症(甲亢)患者感染率,提高患者生活质量。方法 56例甲亢患者经抗甲状腺药物治疗后出现粒细胞缺乏症,按照数字随机数表法将其分为观察组和对照组,每组28例。对照组给予常规升粒细胞治疗,观察组在常规治疗的基础上增加15~30 mg/d泼尼松治疗,观察并比较两组粒细胞恢复正常时间、住院时间和感染率发生情况以及药物所致不良反应。结果观察组粒细胞恢复正常时间和住院时间短于对照组,差异具有统计学意义(P<0.05);观察组感染率为10.71%(3/28),对照组为7.14%(2/28),比较差异无统计学意义(P>0.05),两组血压升高、消化道症状等不良反应例数比较差异无统计学意义(P>0.05)。结论糖皮质激素治疗抗甲状腺药物致粒细胞缺乏症,疗效显著,值得临床推广。     

1例甲巯咪唑致严重粒细胞缺乏症及肝损害的诊治分析

目的:对我院1例甲巯咪唑致甲亢患者严重粒细胞缺乏症及肝功能损害的诊治进行分析总结.方法:停用抗甲亢药物甲巯咪唑,及时给予升白细胞药物、保肝药物、激素等综合措施,病情稳定后予碘131治疗.结果:甲巯咪唑导致的粒细胞减少及肝损害可以有效治疗.结论:抗甲亢药物首次服用后,应短期内密切观察外周血白细胞计数及肝功能,及时防止严重粒细胞缺乏症及肝功能损害发生发展.     

急性粒细胞缺乏症36例治疗体会

目的了解急性粒细胞缺乏症的治疗效果。方法对36例不同原因引起的急性粒细胞缺乏症患者,发病后即采取加强基础护理、早期经验性广谱抗生素、应用造血生长因子rhG-CSF及静脉输注丙种球蛋白、成分输血等综合措施积极抢救。结果36例患者治疗成功34例,有效率达94.4%。结论急性粒细胞缺乏症起病急,病情凶险,但只要及时处理,抢救措施得当,预后较好。     

1例甲巯咪唑致粒细胞缺乏伴发热甲亢患者的临床药学监护

目的为临床合理用药提供参考。方法收集临床药师参与的1例甲巯咪唑致粒细胞缺乏伴发热甲亢患者的临床资料,分析其药物治疗方案的合理性,并开展药学监护。结果患者的药物治疗方案基本合理;且对其开展药学监护后,其用药依从性得到提高,药物治疗方案得到优化。结论临床药师在甲巯咪唑致粒细胞缺乏伴发热患者的临床治疗过程中,充分利用自身药学专业特长,提升了合理用药水平,可更好地为临床和患者服务。     

Agranulocytosis associated with procainamide therapy--report of a case

The case of a 69-year-old woman with procainamide-induced agranulocytosis is reported, and literature reports of 14 other such cases are reviewed. The patients was exposed to procainamide, prescribed for atrial fibrillation, for 26 days, with a daily dose of 1.5 to 4 g and a total dose of 57.5 g. She recovered from agranulocytosis after discontinuation of the drug and hospital treatment for 16 days. Among the reported cases of procainamide-induced agranulocytosis, the daily dosage ranged from 750 mg to 4.5 g; the total ingested dose before agranulocytosis was observed ranged from 36.5 to 316.3 g. Patients treated with procainamide should be instructed to report any soreness of the mouth, throat or gums; unexplained fever; or any symptoms of upper respiratory tract infection. If white blood cell counts indicate bone marrow depression, the drug should be withdrawn and appropriate evaluation begun at once.     

A second trial of clozapine in a case of granulocytopenia

It is generally believed that agranulocytosis, a major problem with clozapine treatment, will tend to occur dose-dependently once it develops in an individual. Therefore, despite clinical progress obtained, the drug has to be discontinued and treatment shifts to another drug. We report on the case of a 29-year-old woman with DSM-IV undifferentiated schizophrenia who developed agranulocytosis after 5 years of 300 mg/day clozapine treatment. The drug was withdrawn and two trials with thioridazine and olanzapine were unsuccessful. Four months after clozapine suspension, we decided to make a further trial, reintroducing clozapine titrated up to 500 mg/day. The patient's symptoms improved and blood leukocytes remained within the normal range after eight months. Copyright 2000 John Wiley & Sons, Ltd.     

Drug-induced agranulocytosis in the Berlin case–control surveillance study

Purpose

Drug-induced agranulocytosis (DIAG) is a rare but serious adverse drug reaction. The Berlin Case–Control Surveillance Study (FAKOS) aimed to identify pharmaceuticals with an increased risk for this condition.

Methods

Adult patients with acute non-chemotherapy–induced agranulocytosis, developed in hospital or in the outpatient setting, were ascertained by active surveillance in all 51 Berlin hospitals between the years 2000 and 2010. Applying the criteria of the World Health Organization, a standardized drug causality assessment was conducted for each agranulocytosis patient to determine possible drug aetiology. Drug risks were quantified in a case–control design with unconditional logistic regression analysis.

Results

Sixty-three out of 88 validated cases of agranulocytosis were identified as being at least probably drug-related. Drug causality assessment resulted in 36 pharmaceuticals with a certain or probable relationship to agranulocytosis. Drugs involved in ≥ 3 cases with a probable or certain causality were metamizole (dipyrone) (N?=?10), clozapine (N?=?6), sulfasalazine (N?=?5), thiamazole (N?=?5), and carbamazepine (N?=?3). In case–control analysis, six drugs were identified with significant odds ratios for DIAG. The highest odds ratios were observed for clozapine, sulfasalazine, and thiamazole.

Conclusions

Our findings are generally in agreement with those of earlier case–control studies. The spectrum of drugs causing acute agranulocytosis has not changed considerably over recent years, despite many newly marketed drugs. Evidence for induction of agranulocytosis by some new pharmaceuticals is supported.     

Risk of drug-induced agranulocytosis: the case of calcium dobesilate

BACKGROUND: In the last 20 years, some cases of agranulocytosis associated with calcium dobesilate consumption in Spain have been reported. A high risk of dobesilate-associated agranulocytosis (121 cases per million per year) calculated using both a case-control and a case-population strategy has been published. However few spontaneous reports have been noted in the same period of time. No explanation exists for this disagreement. METHODS: Estimated incidence rates of agranulocytosis in the IAAAS study and the calculated risk of dobesilate-associated agranulocytosis were used as background risks in a Poisson-based methodology, to calculate the number of coincidental reports of agranulocytosis among patients treated with dobesilate. The influence of treatment duration, notification rate and population characteristics were calculated. RESULTS: During the period 1978-2000, a total of 23 cases would have taken place if the background risk of agranulocytosis were 4.7 per million per year (IAAAS's risk); however, only 9 spontaneous cases of agranulocytosis associated to dobesilate were noted. A simulation showed that with notification rates equal to or higher than 17%, it was not possible to exclude that the 9 cases were false-positives. With notification rates equal or inferior to 16%, it would be unlikely that cases of agranulocytosis were noted in this population with a risk of 4.7 per million per year; therefore, it is necessary to assume a higher agranulocytosis risk. More than 1 case per year could be a false-positive if the background risk of agranulocytosis is 9.5 per million per year, this being the appropriate risk for a population of patients older than 60 years. The duration of treatment beyond 30 days increases the probability of a random coincidence of the intake of drug and an agranulocytosis event. CONCLUSIONS: The disagreement between calculated dobesilate-associated agranulocytosis risk and the number of noted spontaneous reports may be explained by at least three different factors: under-reporting, duration of treatment and age of patients. It is possible, with the methodology presented, to estimate the influence of these factors to avoid confusion with possible false-positive cases and then to design the correct prospective trial that can provide the true agranulocytosis risk.     

Dapsone-mediated agranulocytosis: risks, possible mechanisms and prevention

Agranulocytosis is a rare, severe and unpredictable idiosyncratic reaction associated with drug therapy that can lead to life-threatening illness. Typically, the patient presents with a fever and evidence of infection 1-3 months after initiation of drug administration with a neutrophil count below 0.5x10(9) l. Of the drugs linked with this disease, aminopyrine, dipyrone, clozapine, anti-thyroid agents, sulphonamides and dapsone are the best documented. Generally, agranulocytosis is associated with older individuals (>60 years) and those of non-Caucasian descent. The incidence of agranulocytosis in subjects taking oral dapsone in combination with maloprim for malaria is 1 -- 10-20,000 while leprosy patients treated with dapsone exhibit virtually zero risk of agranulocytosis. However, dapsone is unusual in that during the rare but severe inflammatory disease, dermatitis herpetiformis (DH), the risk of agranulocytosis is multiplied between 25 and 33 fold compared with normal patients. It is conceivable that dapsone might exhibit a similar risk in coeliac disease, a condition related to DH. As dapsone plasma levels in DH subjects can be high (2-10 microg/ml) the increased risk of agranulocytosis could be related to drug dosage, or increased immune responsiveness. The high risks in DH patients probably necessitate monitoring of neutrophil cell population in the first 3 months of therapy, while topical usage of the drug in acne treatment in otherwise healthy patients predominantly below the age of 25 is at the opposite end of the risk scale, probably as low as 1 in 10-20,000 patients.     

Haematological toxicity of drugs used in psychiatry

Almost all classes of psychotropic agents have been reported to cause blood dyscrasias. Mechanisms include direct toxic effects upon the bone marrow, the formation of antibodies against haematopoietic precursors or involve peripheral destruction of cells. Agranulocytosis is probably the most important drug-related blood dyscrasia. The mortality from drug-induced agranulocytosis is 5-10% in Western countries. The manifestations of agranulocytosis are secondary to infection. Aggressive treatment with intravenous broad-spectrum antimicrobials and bone marrow stimulants may be required. Of drugs encountered in psychiatry, antipsychotics including clozapine (risk of agranulocytosis approximately 0.8%, predominantly in the first year of treatment) and phenothiazines (chlorpromazine agranulocytosis risk approximately 0.13%), and antiepileptics (notably carbamazepine, neutropenia risk approximately 0.5%) are the most common causes of drug-related neutropenia/agranulocytosis. Drugs known to cause neutropenia should not be used concomitantly with other drugs known to cause this problem. High temperature and other indicators of possible infection should be looked for routinely during treatment. Clozapine is well known as a drug that can cause blood dyscrasias, but olanzapine and other atypicals may also cause similar problems. In addition to genetic factors, there are likely to be dose-related and immunological components to these phenomena. Important lessons have been learnt from the haematological monitoring that is necessary with clozapine and the monitoring has been very successful in preventing deaths related to clozapine-induced agranulocytosis. Continuing research into the mechanisms of drug-induced neutropenia and agranulocytosis may serve to further enhance the safe use not only of clozapine, but also of other agents.     

Agranulocytosis associated with calcium dobesilate

OBJECTIVE: Calcium dobesilate is used in the treatment of diabetic retinopathy, chronic venous insufficiency, haemorrhoids and other ill-defined vascular conditions. It has been associated with agranulocytosis in anecdotal reports. We describe the clinical course of a series of patients who developed agranulocytosis while taking this drug, and we estimate the risk by means of both a case-control and a case-population strategy. METHODS: All cases of agranulocytosis meeting strict predefined diagnostic criteria in an area of 3.3 to 3.9 x 106 inhabitants in the period 1980-1998 were identified. Cases and age-, gender- and hospital-matched controls were interviewed with a structured questionnaire including a detailed drug history. Each case was reviewed and confirmed by a haematologist, who was blind with respect to drug exposures. Consumption data were used to estimate the risk of agranulocytosis associated with calcium dobesilate using a case-population approach in which the incidence of agranulocytosis among users of calcium dobesilate was compared with that among the non-exposed population. RESULTS: After a follow up of 68.55 x 10(6) person-years, 345 cases of agranulocytosis (242 community cases) were assembled. Reliable information was obtained from 216 cases. Two patients exhibited positive rechallenge. Twelve cases (5.6%) and 5 of 1380 controls (0.4%) had taken calcium dobesilate in the week before. With the case-control approach, the odds ratio was 23.66 [95% confidence interval (CI), 7.54-74.24], the attributable risk was 5.3% (95% CI, 3.0-9.4), and the number of cases attributable to dobesilate in the study area during the study period was 12.8. The case-population estimates were an incidence of 121.03 cases per 10(6) patient-years, a relative risk of 39.55 (95% CI, 17.96-77.49), an attributable risk of 6.73% (CI 3.4-12.9), and 16.30 cases attributable to dobesilate in the study area during the study period. DISCUSSION: This study adds to evidence indicating that the case-population method is adequate for the study of rare type B adverse drug reactions. An additional advantage of this approach is that the incidence of the disease of interest among those exposed to the drug can be estimated. The risk of agranulocytosis associated with calcium dobesilate should be considered in relation to poor evidence of its clinical efficacy.     

硫唑嘌呤治疗视神经脊髓炎谱系病致1例粒细胞缺乏的分析

对硫唑嘌呤治疗视神经脊髓炎谱系病（NMOSD）致1例粒细胞缺乏进行分析,从硫唑嘌呤致造血系统损害的临床特点、发生率、不良反应预防、基因多态性以及NMOSD患者粒细胞缺乏的治疗措施等方面进行分析和讨论,为临床有效、安全用药提供参考。